Over the past decade there has been a substantial expansion of opioid analgesic use for patients who have chronic pain. The misuse of prescription opioid analgesics, however, is a growing public health problem and opioid medications have surpassed cocaine and heroin as the leading drugs of abuse. Chronic pain is another important public health problem that affects over 50 million Americans and costs over $70 billion per year in health care expenses, disability, lost wages and productivity. The incidence and prevalence of opioid misuse in patients treated for chronic pain is unclear and little is known about the factors predisposing chronic pain patients to opioid misuse. Even less is known about behavioral contingencies associated with the development of aberrant opioid-use behaviors, but some basic operant conditioning processes are likely to be involved. Specifically, negative reinforcement principles may shape early opioid-use behaviors in patients with chronic pain, potentially increasing the likelihood of opioid misuse. Pain is an intrinsically aversive stimulus, and in patients with chronic pain this aversive stimulus is present most, if not all of the time. Prescription opioid medications (especially shorter acting preparations) provide for a quick but temporary reduction or elimination of the aversive stimulus and thus medication-taking behaviors are negatively reinforced. A subset of chronic pain patients learn that taking more opioid medication than prescribed, or taking them more frequently than prescribed, results in longer periods of pain relief and/or greater pain reduction. There is very little information available regarding basic neural mechanisms involved in this avoidance-learning of pain-relieving behaviors. Despite recent advances in neuroimaging technologies and development of fMRI-based human learning models, few if any models for studying negative reinforcement in the scanning environment are available. Given the widespread problem of chronic pain in the United States, increasing use of prescription opioids for the treatment of chronic pain, and the rising problem of opioid misuse, reliable and valid models are needed to begin elucidating neural processes involved in negative reinforcement in the context of chronic pain. The Investigators propose to further develop and test a unique human model of negative reinforcement in the context of pain to identify key brain areas associated with negative reinforcement of pain-avoidance behaviors. Participants from 3 cohorts (healthy adults, patients with chronic pain and a history of opioid abuse/dependence, and patients with chronic pain on opioid therapy and no history of opioid abuse/dependence) will undergo an fMRI session during which they will receive blocks of tonic, thermal pain stimuli. They will be tasked with learning a behavior to turn-off the thermal pain (negative reinforcement learning). Brain areas associated with different aspects of negative reinforcement learning in the context of pain will be examined. Findings from this study could help in the early identification of patients that might be at risk for opioid misuse, and could lead to the development of new interventions for opioid prescription misuse. PUBLIC HEALTH RELEVANCE: Prescription opioid misuse has increased dramatically over the past decade and opioid medications have surpassed cocaine and heroin as the leading drugs of abuse. Little is known about the factors predisposing chronic pain patients to opioid misuse in the outpatient setting. Negative reinforcement principles may shape early opioid-use behaviors in patients with chronic pain potentially increasing the likelihood of opioid misuse, abuse and addiction. We propose to develop and test a unique, human model of negative reinforcement in the context of pain avoidance, and subsequently use that model to explore the neural mechanisms of addiction to pain medication.